TRAF2
Description
The TRAF2 (TNF receptor associated factor 2) is a protein-coding gene located on chromosome 9.
TNF receptor-associated factor 2 is a protein that in humans is encoded by the TRAF2 gene.
== Function == The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from members of the TNF receptor superfamily. This protein directly interacts with TNF receptors, and forms complexes with other TRAF proteins. TRAF2 is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-κB. The protein complex formed by TRAF2 and TRAF1 interacts with the IAP family members cIAP1 and cIAP2, and functions as a mediator of the anti-apoptotic signals from TNF receptors. The interaction of this protein with TRADD, a TNF receptor associated apoptotic signal transducer, ensures the recruitment of IAPs for the direct inhibition of caspase activation. cIAP1 can ubiquitinate and induce the degradation of this protein, and thus potentiate TNF-induced apoptosis. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of only one transcript has been determined.
TRAF2 regulates the activation of NF-κB and JNK, playing a crucial role in controlling cell survival and apoptosis. It is essential for the normal antibody isotype switch from IgM to IgG. TRAF2 acts as an E3 ubiquitin-protein ligase, promoting 'Lys-63'-linked ubiquitination of target proteins including BIRC3, RIPK1, and TICAM1. As a key component of several E3 ubiquitin-protein ligase complexes, TRAF2 facilitates the ubiquitination of target proteins by bringing them into proximity with other E3 ubiquitin ligases. It regulates the levels of BIRC2 and BIRC3 proteins by inhibiting their autoubiquitination and subsequent degradation, a process independent of the TRAF2 RING-type zinc finger domain. TRAF2 mediates the activation of NF-κB by EIF2AK2/PKR. In association with BIRC2 or BIRC3, it promotes the ubiquitination of IKBKE.
TRAF2 is also known as MGC:45012, RNF117, TRAP, TRAP3.
Associated Diseases
- ovarian cancer
- esophageal cancer
- 22q11.2 deletion syndrome
- pyknoachondrogenesis
- T-B+ severe combined immunodeficiency due to JAK3 deficiency
- familial primary pulmonary hypoplasia
- severe combined immunodeficiency due to LAT deficiency
- immunodeficiency 73c with defective neutrophil chemotaxis and hypogammaglobulinemia
- immunodeficiency 105
- immunodeficiency 99 with hypogammaglobulinemia and autoimmune cytopenias
